EP0370097A1

EP0370097A1 - Therapeutic material for covering wounds and skin lesions and process for the preparation thereof

Info

Publication number: EP0370097A1
Application number: EP89906189A
Authority: EP
Inventors: Zoltán KALISZKY; Istvan Czappan; Gizella Miholics; Marta Kovacs; Gyula Sebestyen; Anna Zavodszkyne Szabo
Original assignee: Licencia Talalmanyokat Ertekesito Es Innovacios Kuelkereskedelmi Vallalat; Licencia Talalmanyokat Ertekesito Vallalat
Current assignee: Licencia Talalmanyokat Ertekesito Es Innovacios Kuelkereskedelmi Vallalat; Licencia Talalmanyokat Ertekesito Vallalat
Priority date: 1988-05-30
Filing date: 1989-05-30
Publication date: 1990-05-30
Also published as: WO1989011879A1; DK19990A; KR900701327A; JPH03500853A; AU3693989A; FI900422A0; DK19990D0; AU616769B2

Abstract

L'invention concerne une matière thérapeutique destinée à recouvrir des blessures et des lésions cutanées ainsi que la préparation de ladite matière. La matière thérapeutique selon l'invention contient un support imprégné ou recouvert d'une émulsion non irritante que l'on peut facultativement mélanger avec une quantité efficace de matière biologiquement active. La matière thérapeutique recouvrant les blessures ne colle pas à la surface, est perméable aux sécrétions et facile à manipuler.The invention relates to a therapeutic material intended to cover wounds and skin lesions as well as the preparation of said material. The therapeutic material according to the invention contains a support impregnated or covered with a non-irritating emulsion which can optionally be mixed with an effective quantity of biologically active material. The therapeutic material covering the wounds does not stick to the surface, is permeable to secretions and easy to handle.

Description

Therapeutic material for covering wounds and skin lesions and process for the preparation thereof

The invention relates to therapeutic material for covering wounds and skin lesions and for the process for the preparation thereof.

According to known methods for treatment of wounds with discharge and injured skin surfaces covering with gauze tapes/sheets, locally impregnated gauze sheets or gauze sheets impregnated with paraffin

(Jelonet^R, a product of Smith and Nephew) are generally used. In cases when the wound had to be treated also with biologically active material, then the drug has been directly applied to the gauze or wound surface at the place and at the time of the treatment, thereafter the wound thus covered has been dressed with bandage. Drawbacks of the known methods are as follows:

- When removing the bandage the newly produced epithelial layer gets damaged, in many cases the surface gets considerably traumatized;

- the secretion dries in the conventional gauze layer, it forms a solid surface, not permeable to the secretion; - the quantity of the optionally used biologically active materials is not optimal owing to the mode of application;

- the sterility cannot be assured in all cases. To eliminate the aforementioned drawbacks the aim of our invention is to provide a therapeutic material for covering wounds and skin. lesions, which

- does not stick in the wounds, - can be removed from the surface after the treatment simply, without any damage and traumatization;

- is preamble to secretion;

- is admixable with any biologically active material i.e. with water soluble, oil soluble or fat soluble active ingredients if desired, and so an optimal active ingredient level can be ensured on the surface to be treated;

- is storable in sterile form for a long time and can be simply used at any time. We have found that when a carrier, suitable for covering wounds and skin lesions, is laminated or impregnated with an emulsion prepared of the mixture of different polyoxyethylene glycols and an oil in the presence of emulsifying agent(s) of o/w type, having particularly high HLB value (e.g. HLB >10) and admixed optionally with an effective amount of a biologically active material, the desired aim can be achieved. Moreover, said solution enables the controlled administration and release of the optionally used active ingredient too. Accordingly the present invention relates to a therapeutic material for covering wounds and skin lesions which comprises a) a carrier made of textile or paper material or synthetic fibre, laminated or impregnated with b) an emulsion having the following composition: propylene glycol 0-20% by weight polyoxyethylene glycols 5-95% " oil 10-25% " emulsifying agent 5-20% " which is optionally admixed with c) an effective amount of biologically active ingredient, selected from antibiotics, antiseptics, desinfectants, antimycotics, biologically active vegetable extracts and dermatologica.

The therapeutic material for covering wounds and skin lesions according to the invention may be prepared by producing an emulsion from the ingredients listed in point b) by method per se by optionally admixing the emulsion obtained with an effective amount of biologically active material according to point c), then impregnating the carrier according to point a) with said mixture, thereafter packing the product obtained and optionally sterilizing.

As a carrier a) woven textile materials of different density, prepared of twisted or monofilament yarn, (e.g. gauze or loose fabrics), or materials without weaving, (e.g. veil fabrics), paper sheets, viscose sheets both optionally perforated or nets and/or foils made of synthetic materials, may be used.

As polyoxyethylene glycols in emulsion b) a mixture of polyoxyethylene glycols of different degree of polymerization (e.g. n=300-6000) is used wherein the ratio of polyoxyethylene glycols of lower and higher degree of polymerization is ranging from (1:40) to (40:1), preferably from (1:1) to (20:1). In the emulsion b) accoring to the invention the oil phase may be any known oil generally used for injection preparations, for example vegetable oils (e.g. sunflower oil, olive oil, peanut oil, linseed oil, castor oil, etc.), animal oils (e.g. fish oil), mineral oils (e.g. paraffin oil), synthetic oils (e.g. silicone oil, types Myritol, Levitol, etc.).

In the emulsion b) according to the invention ionic or non-ionic emulsifying agents of a high HLB value (e.g. HLB>10) may be used, e.g. esters of ethoxylated fatty alcohols, ester prepared from polyhydric alcohols and fatty acids, ethoxylated dianhydrosorbitol-stearates, ethylene oxide adducts, e.g. fatty acid-polyethylene glycols esters, fatty alcohol-ethylene oxide adducts, etc.

The emulsion of o/w type used in the therapeutic material for covering wounds and skin lesions according to the invention makes it possible that optionally any kind of biologically active material, i.e. material being soluble in water, oil or fat, may be admixed with the composition and so the active material may be administered simply to the surface to be treated in an optimal, predetermined amount and the treatment may be carried out by non--qualified persons too.

The product according to the invention may be produced in any size and shape as required, so. e.g. sheets of 13x8cm, 5x6cm and 8x15cm can be prepared. The sheets obtained are placed onto cardboard or polymer sheets and packed by covering with metal or polymer foil and sterilized if desired. The products thus obtained form sterile, closed, easy to handle units.

The products according to the invention are well suitable for treating burn wounds, ulcus crusis, surfacial wounds with purulent discharge and different oozing skin lesions, for covering wounds after plastic operations, for use in ambulatory treatments, in first--aid sets and everywhere where the presence of wound-treating materials is permanently needed, so e.g. in army, on ships or traumatology etc.

The details of the invention are illustrated by the following non-limiting Examples. The suitability of the therapeutic materials according to the invention for applying to the skin is proved by the following biological Examples.

Biological Examples

A) Skin irritation test

The tests were carried out on New-Zeland rabbits. An area, of 5cm² on the back fur of the rabbits was depilated and gauze sheets, each impregnated with 0.5g of the emulsions according to the following Examples 1-10, were applied thereon and bandaged according to common clinical practice.

24 and 48 hours after the teratments the bandages were removed. 3 animals were used per treatment and per test period.

It was established that the gauze sheets could easily be removed in every case, they were not dried in and did not cause any irritation on the skin.

B) Microbiological tests 1) Sterility test

Prior to the skin irritation tests the sterility of the impregnated gauze sheets to be used was checked in the following way: the gauze sheets, having been welded around with PE foil, were sterilized under aseptic conditions in steril box, thereafter cut into pieces of about 1/2cm² by the use of sterile scissors and forceps, thereafter these pieces of gauze were inoculated into sterile liquid soya-casein and Sabouraud culture media. The cultures obtained were incubated at 32°C and 26°C for one week. Thereafter they were evaluated visually and it was found that all gauze sheets were sterile. 2) Microbiological stability test

In this experiment by using two different bacterium strains (Ps"eudomonas aeruginosa and . Staphylococcus aureus), it was tested whether during a supposedly maximal duration of 72 hours of wound--coverage, the applied material did not serve as a culture medium for the microbas being present.

The material serving for impregnation (e.g. any of the emulsions according to Examples 1-10) was infected by the above microorganisms and after an incubation for 24, 48 and 72 hours the number of germs was determined.

It was established that growth could not be observed in case of any of the microorganism strains, on the contrary the initial number of germs (about 10 -10 /g) decreases gradually to a value of 0-10/g. These results show that the emulsions used for impregnation exhibit some microbiological activity too.

Preparation of the emulsion

Example 1 Composition:

Propylene glycol 5 %

Polyoxyethylene glycol 400

(Lutrol 400) 59.5%

Polyoxyethylene glycol 400

(Lutrol 4000) 8.0% Cont. of Example 1

Myritol 318 20.0% Solutol HS 15 7.5%

Example 2 Composition:

Paraffin oil 1% Propylene glycol 10% Lutrol 400 75% Lutrol 4000 10% Cremophor RH 60 4%

Example 3 Composition:

Linseed oil 2% Propylene glycol 4% Lutrol 300 80% Lutrol 6000 8% Cremophor RH 60 6%

Example 4 Composition:

Propylene glycol 5% Lutrol 300 40% Lutrol 1540 35% Myritol 318 10% Cremophor EL 10% Example 5 Composition:

Luvitol EHO 13% Lutrol 400 59.5% Lutrol 4000 18% Cremophor A 6 9.6%

Example 6 Composition:

Silicone oil (300 cp) 5% Lutrol 400 70% Lutrol 1540 10% Cremophor S 9 15%

Example 7 Composition:

Maize oil 15% Lutrol 400 55% Lutrol 4000 10% Solutol HS 15 20%

Example 8 Composition:

Sesame oil 8% Propylene glycol 2% Lutrol 400 70% Lutrol 1540 5% Solutol HS 15 15% Example 9 Composition:

Peanut oil 5%

Lutrol 300 70%

Lutrol 4000 20%

Polypropylene glycol 5%

Solutol HS 15 5%

Example 10 Composition:

Sunflower oil 6%

Lutrol 300 80%

Lutrol 6000 2%

Solutol HS 15 12%

The emulsion according to the above Examples 1-10 may be prepared by method known perse, e.g. by melting the different polyoxyethylene glycols and admixing the melt obtained under stirring with the other ingredients.

The chemical composition of the above materials specified by trade marks as follows:

Myritol 318: caprilicacid-capric acid-trigliceride Solutol HS 15: diethylene glycol-monoethyl ether Cremophor RH 60: polyethylene (660)-12-hydroxy¬

-stearate (60) Cremophor EL: polyoxyethylene glycerol¬

-triricinoleate (35) Cremophor A 6 mixture of ethoxylated fatty alcohols and free fatty alcohols

Cremophor S 9 polyethylene glycol(400)-stearate

Preparation of materials for covering wounds

Example 11

Onto a polypropylene foil containing holes of a size of 6x6cm a loose-woven gauze sheet is arranged thereafter the gauze sheet is impregnated with the emulsion according to Example 1, then it is covered with a metal foil, cut into pieces and sterilized by radiation.

Example 12

The procedure of Example 11 is followed, with the difference that an effective amount of gentamycin as active ingredient is suspended in the emulsion before impregnation.

Example 13

The procedure of Example 11 is followed, with the difference that a perforated sheet made of synthetic material (e.g. polypropylene, polyamide, viscose etc.) is used as a carrier.

Example 14

The procedure of Example 12 is followed, with the difference that one of the following ingredients is used in an effective amount: erithromycin, neomycin, sisomycin, tetrane; chlorohexidine gluconate, benzalconiumchloride, micanozole or metronidazole.

Claims

What we claim is :

1. Therapeutical material for covering wounds and skin lesions characterized by containing a) a carrier made of textile or paper or synthetic fibre, impregnated or laminated with b) an emulsion of the following composition: propylene glycol 0-2% by weight polyoxyethylene glycols 5-95% " oil 10-25% " emulsifying agent(s) 5-20% " which emulsion is optionally admixed with c) an effective amount of biologically active materials selected from antibiotics, antiseptics, dezinfectants, antimycotics, biologically active vegetable extracts, dermatologica.

2. Therapeutical material according to Claim 1 characterized in that the support material a) is a textile fabric of different density and made of twisted or monofilament yarn, preferably gauze or loose cotton fabric.

3. Therapeutical material according to Claim 1, characterized in that the carrier a) is a perforated viscose sheet or a net made of synthetic fibre.

4. Therapeutical material according to Claim 1, characterized in that the emulsion b) contains as an oil a vegetable oil, e.g. sunflower oil, olive oil, maize oil, peanut oil, linseed oil, animal oil, e.g. fish oil, synthetic oil, e.g. silicone oil (10-10000 cp) or mineral oil, e.g. paraffine oil.

5. Therapeutical material according to Claim 1, characterized in that in the emulsion b) the polyethoxyethylene glycols comprises a mixture of polyoxyethylene glycols of different degree of polymerization (e.g. n=300-6000) and the ratio of polyoxyethylene glycols of lower and higher degree of polymerization is in the range from (1:40) to (40:1), preferably from (1:1) to (20:1).

6. Therapeuticalmaterial according to Claim 1, characterized by optionally containing a biologically active material c) selected from gentamycin, erithromycin, neomycin, risomycin, tetrane; chlorohexidinegluconate, benzalconium chloride; micanozole and metronidozole.

7. Process for the preparation of therapeutical material for covering wounds and skin lesions according to Claim 1, c h a r a c t e r i z e d by preparing emulsion b) admixing the ingredients, optionally admixing the emulsion obtained with an effective amount of biologically active material c) laminating said emulsion on carrier a) or impregnating by same and packing the product obtained and sterilizing if desired.